Treatment With l-cis Diltiazem Before Reperfusion Reduces Infarct Size in the Ischemic Rabbit Heart In Vivo

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Abstract

<I>l-cis</I> Diltiazem, an optical isomer of diltiazem, protects against myocardial dysfunction in vitro, whereas its Ca<SUP>2+</SUP> channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidence that <I>l-cis</I> diltiazem actually protects against ischemia/reperfusion injury in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 min. Treatment with diltiazem before and during ischemia (bolus 200 μg/kg and 15 μg/kg per minute for 25 min, i.v.; 575 μg/kg total) showed slightly depressed hemodynamic parameters, while <I>l-cis</I> diltiazem (1150 μg/kg) had no effect. Treatment with <I>l-cis</I> diltiazem produced a high recovery of the thickening fraction and limited the infarct size in a dose-dependent manner. Furthermore, the treatment with <I>l-cis</I> diltiazem (1150 μg/kg) or diltiazem (575 μg/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that <I>l-cis</I> diltiazem affects some events in the onset of reperfusion, independently of Ca<SUP>2+</SUP>-channel-blocking action. Our observations are the first to show that <I>l-cis</I> diltiazem demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 80(4), 319-325, 1999-08-01

    The Japanese Pharmacological Society

References:  20

Codes

  • NII Article ID (NAID)
    10008195710
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4836994
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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